Prostate cancer is the second leading cause of cancer deaths in men, with approximately 27,000 deaths and 234,000 new cases expected this year in American men. Prostate cancer arises in the prostate, an approximately walnut-sized gland found in the male reproductive system which is responsible for the generation and storage of seminal fluid. The prostate contains many small glands which make about twenty percent of the fluid comprising semen. In prostate cancer, the cells of these prostate glands are transformed into cancer cells. Because the prostate surrounds part of the urethra, prostate diseases often affect urination, ejaculation, or defecation.
Because prostate cancer begins when normal semen-secreting prostate gland cells undergo transformation into cancer cells, prostate cancer is classified as an adenocarcinoma, or glandular cancer. The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, resulting in a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Over time, these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor. Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or the tumor cells may develop the ability to travel in the bloodstream and lymphatic system. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder.
Screening for prostate cancer generally involves either digital rectal examination or prostate specific antigen (PSA) test. During a digital rectal examination, the health care provider checks the size, shape, and texture of the prostate for areas which are irregular, hard or lumpy, which may be indicative of prostate cancer. The PSA test measures the blood level of prostate-specific antigen, an enzyme produced by the prostate. PSA levels under 4 ng/mL are generally considered normal; PSA levels between 4 and 10 ng/mL indicate a risk of prostate cancer higher than normal, but the risk does not seem to rise within this six-point range. When the PSA level is above 10 ng/mL, the association with cancer becomes stronger.
While the measurement of serum PSA assay has proven to be a very useful diagnostic tool, the utility of the PSA test has limitations. For instance, PSA testing is not able to reliably identify early-stage disease. Similarly, there is no marker available for predicting the emergence of the typically fatal metastatic stage of the disease. Diagnosis of metastatic prostate cancer is achieved by open surgical or laparoscopic pelvic lymphadenectomy, whole body radionuclide scans, skeletal radiography, and/or bone lesion biopsy analysis. Clearly, better imaging and other less invasive diagnostic methods offer the promise of easing the difficulty those procedures place on a patient, as well as improving therapeutic options. Accordingly, there is a need for reagents that are capable of reliably identifying early-stage disease, predicting susceptibility to metastasis, and precisely imaging tumors to assist in the treatment, diagnosis, prognosis, and management of prostate cancer. The present invention satisfies these and other needs.